POTASSIUM PERMEABILITY ACTIVATED BY INTRACELLULAR CALCIUM-ION CONCENTRATION IN THE PANCREATIC BETA-CELL

Abstract

Membrane potentials and input resistance were measured in .beta.-cells from mouse pancreatic islets of Langerhans in a study designed to assess the role of a K permeability specifically blocked by quinine or quinidine and activated by intracellular calcium ion concentration ([Ca2+]i-activated PK). Addition of 100 .mu.M-quinine to the perifusion medium resulted in a 10-30 mV depolarization of the membrane and an increase in the input resistance of about 4.707 .OMEGA.. In the absence of glucose, 100 .mu.M-quinine induced electrical activity. In the presence of glucose, 100 .mu.M-quinine abolished the burst pattern of electrical activity and very much reduced the graded response of spike frequency normally seen with different concentrations of glucose. Addition of mitochondrial inhibitors, KCN, NaN3, DNP [2,4-dinitrophenol], CCCP [carbonyl-cyanide, m-chlorophenylhydrazone], FCCP [p-tri-fluoromethoxyphenylhydrazone], to the perifusion medium containing glucose rapidly hyperpolarized the .beta.-cell membrane, inducing a concomitant decrease in input resistance. In the presence of glucose, these mitochondrial inhibitors reversibly blocked electrical activity; upon removal of the inhibitor, recovery of electrical activity followed a biphasic pattern. The effects of mitochondrial inhibitors were partially reversed by 100 .mu.M-quinine. The membrane potential of the .beta.-cell in the absence of glucose is predominantly controlled by the [Ca2+]i-activated PK. This permeability to K may control the level for glucose stimulation and lead to the generation of the burst pattern.